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Taking small steps towards targets perspectives for clinical practice in diabetes, cardiometabolic disorders and beyondTaking small steps towards targets – perspectives forclinical practice in diabetes, cardiometabolic disordersand beyond A. Golay,1 E. Brock,2 R. Gabriel,3 T. Konrad,4 N. Lalic,5 M. Laville,6 G. Mingrone,7 J. Petrie,8T.-M. Phan,9 K. H. Pietil€ainen,10,11 C.-H. Anderwald12,13,14 Big changes are hard. When trying to achieve guideline targets in diabetes and Literature review of the effects of change in cardiometabolic disorders, patients can lack commitment or suffer despondency. It multiple lifestyle and metabolic parameters towards is much easier to make small changes in lifestyle or treatment, which are less outcomes in cardiometabolic diseases. Identification of the benefits of small change and author noticeable and easier to manage long-term. Obesity is central to the cardiometa- perspectives on the impact for clinical practice.
bolic disorders, and even small weight losses of 2–5% can improve the cardiomet- abolic risk profile and substantially reduce the risk of developing type 2 diabetes.
Likewise, small increases in physical activity, such as 15 Small changes in individual lifestyle and metabolic per day, can cut the risk of heart disease by 10%. Lifestyle or treatment changes parameters can result in significant beneficial that lead to small improvements in metabolic parameters also impact patient out- effects, but a major impact can occur when small come – for example, a 5 mmHg decrease in blood pressure can translate into sig- changes are made together in multiple parameters.
nificant reductions in the rates of myocardial infarction and cardiovascular The physician should recognise their influence to motivate and encourage change in patients, one mortality. Benefits of small changes can also be seen in health economic outcome small step at a time towards guideline targets.
models. Implementing change at an individual versus a population level has differ- ent implications for overall benefit and patient motivation. Even very small steps taken in trying to reach guideline targets should represent a positive achievement Universite Lyon, Hospices Civilsde Lyon-1, Lyon, France for patients. Patient engagement is essential – only when patients commit them- selves to change can benefits be maintained, and physicians should recognise their influence. Small changes in individual parameters can result in significant beneficial effects; however, a major impact can occur when small changes are made Rome, Italy8Institute of Cardiovascular and together in multiple parameters. More research is required to elucidate the full impact of small changes on patient outcome.
Glasgow, Glasgow, UK9Novo Nordisk Region EuropeA/S, Z€urich, Switzerland Here, we offer the perspectives of a panel of experts in the field of cardiometabolic disorders and diabetes, The evidence base for each clinical practice guideline who met in November 2011 to discuss the influence is built on proven trial outcomes; however, ‘real-life’ on patient outcomes of ‘small change’ in a variety of Helsinki University CentralHospital and University of patients do not necessarily reflect study cohorts and lifestyle and metabolic parameters. Each author per- are subject to influences outside of the realm of the formed a review of relevant literature for their chosen clinical trial. Target values for clinical measurements, lifestyle or metabolic parameter, based on PubMed Medicine Finland (FIMM),University of Helsinki, Helsinki, as defined in clinical practice guidelines, are ‘ideal’ searches and accompanying appraisal of medical goals to be reached by patients, but these goals can abstracts services (MedScape), medical reports and sometimes seem unachievable, and patients may lack press releases, up to November 2011. Additional litera- Medicine – Endocrinology andMetabolism, General Hospital commitment, or suffer despondency, when trying to ture searches using the same resources were performed reach them. Big changes are hard. It is much easier when drafting the manuscript, up to April 2012.
to make small changes in lifestyle and treatment pat- The aim of this review was to present the available Agathenhof, Micheldorf, Austria14Istituto di Ingegneria terns, which are less noticeable and easier to manage evidence for the impact of small changes in cardio- long-term. But what impact do small changes have, metabolic disorder management, and to discuss the and how can small changes help to achieve bigger clinical practice implications for these patients and Int J Clin Pract, April 2013, 67, 4, 322–332. doi: 10.1111/ijcp.12114 reductions in hepatic steatosis, respectively (6).
Small weight losses may also lower mortality rates. A Professor Alain Golay,University Hospital Geneva, 12-year, US study of weight loss in overweight indi- Visceral obesity is central to the cluster of metabolic viduals with diabetes showed an average 25% reduc- Teaching for Chronic Diseases,4, rue Gabrielle Perret-Gentil, abnormalities constituting the metabolic syndrome, tion in total mortality (28% in CVD- and diabetes- which increase the risk of developing a number of related mortality) in those subjects who intentionally diseases including type 2 diabetes mellitus (T2DM), lost weight (7). However, even small weight losses cardiovascular disease (CVD) and cancer (1). There (0.5–4 kg) showed a clearly reduced mortality risk have been five major intervention trials that have studied the impact of weight loss through lifestyleinterventions (healthier diet and greater exercise) on Effect of small changes in diet and exercise on the risk of developing T2DM (2). These trials all showed a striking reduction in the risk of T2DM (of Changes to diet can be quantitative (calorie intake 42–67%) with intervention, compared with control restriction) and qualitative (shift in macronutrient groups, despite moderate weight reductions of 0–5.6 kg.
distribution), but in terms of weight loss, decreased Of these trials, the United States (US) Diabetes energy intake appears to have the most impact (8). A Prevention Program (DPP) showed that for every meta-analysis of 12 studies that assessed the effect of kilogram lost, the risk of developing T2DM for sub- jects with impaired glucose tolerance (IGT) was restriction, or a ‘low-fat’ diet) on weight change over reduced by 16% (2). The metabolic syndrome has 36 months in patients with obesity and cardiometa- also been associated with twice the risk of coronary bolic syndrome suggested an approximate 5 kg loss heart disease (CHD) versus matched controls, with over the first 12 months, followed by a 6-month the presence of even one or two cardiometabolic syn- relapse (reverting to close to baseline weight) before drome risk factors increasing the risk of mortality an average 3 kg loss from 18 to 36 months (9).
(3). Thus, weight loss is a common and important While this overall weight loss was low, it was accom- panied by reductions in SBP and DBP and improve- How should we define a ‘small’ change in body ments in circulating lipids. The recent DEWL trial weight? In terms of absolute loss, 5 kg would appear explored the effects of a reduced calorie diet (low- to be ‘small’, but in real terms this would depend on fat, with an increased proportion of carbohydrate or the baseline weight (i.e. a small change for a person protein) in overweight subjects with T2DM (10). The of 130 kg, but relatively much greater for a person of participants lost a small amount of weight (2–3 kg) 80 kg). Therefore, percentage loss may be the best over the 2-year study, but compared with baseline, measure, and a 2–3% loss could be considered a significant reductions in HbA1c were seen after 6 months, and total cholesterol had decreased by Weight loss can lead to collective improvements in study end (10). Nutritional changes to diet also seem several cardiometabolic risk factors; indeed, a linear to have an impact on patient outcomes. A study relationship has been noted between weight losses of investigating the effect of a Mediterranean diet (high 2–15% and reductions in glycated haemoglobin in fruits, vegetables, fish and olive oil) versus a ‘low- (HbA1c), systolic and diastolic blood pressure (SBP/ fat’ diet in newly diagnosed T2DM patients showed a DBP) and triglycerides (TG), plus improvements in similar moderate weight loss in each group after the circulating cholesterol profile (high- and low- 4 years (3.8 kg vs. 3.2 kg, respectively) but those on density lipoprotein, HDL/LDL) (4). Even with small the Mediterranean diet had a far higher probability weight losses of 2–5%, positive changes in these of remaining free from anti-hyperglycaemic therapy, parameters could be observed. The beneficial effects and benefitted from greater HbA1c reduction and of weight loss may also be long-lasting, showing a lower BP and TG levels (11). Likewise, a more recent ‘legacy effect’. Results from the 10-year follow-up of study of the effects of a Mediterranean diet on inci- the US DPP demonstrated that whilst weight loss dence of T2DM in subjects with at least three CVD risk was greater in the ‘lifestyle intervention’ versus the factors demonstrated a 52% reduction in the incidence metformin group only for the first 4 years, the 10- of T2DM, compared with a ‘low-fat’ diet, despite year incidence of T2DM was reduced by 34% versus insignificant mean changes in weight (0.2–0.6 kg) placebo with lifestyle intervention, compared with a Physical inactivity is associated with twice the risk Additionally, weight loss leads to a disproportion- of heart disease, compared with active people (13). A ate reduction in hepatic fat, with losses of 1–5%, 5–10% 2006 World Health Organization survey found that and > 10% corresponding to 33%, 65% and 80% only around 30% of European populations over Int J Clin Pract, April 2013, 67, 4, 322–332 15 years of age were sufficiently active (13), suggest- ing a high risk of a future ‘CHD epidemic’, with (~ 13 min/day) had a 14% reduced risk of all-cause potential impact on European health care budgets.
mortality and a 3-year longer life expectancy (20).
Disparities in levels of physical activity have also Each additional 15 min of exercise per day further been noted between different racial/cultural groups, reduced all-cause mortality by 4%. These benefits were applicable to all age groups and both sexes, as The US DPP set the lifestyle intervention partici- well as those with cardiovascular risk factors (20).
pants the specific goals of 7% weight loss, con- Since physical activity cannot easily be analysed sumption of no more than a quarter of their daily independently of other variables, such as weight loss, calories from fat (300–450 kcal), and at least in these intervention trials, it is difficult to assess its 150 min of physical activity per week (15). After impact. However, a meta-analysis of trials studying 24 weeks, 50% of the participants had achieved the the effect of aerobic exercise, resistance training or a weight loss goal, and 74% had reached the physical combination of both in T2DM patients revealed that activity target. Over the first 4 years, the average 12 weeks of training (for 90–300 min/week) was weight loss in the lifestyle intervention group was associated with a 0.8% mean reduction in HbA1c and 5.6 kg, versus 2.1 kg in the metformin comparator small-to-moderate benefits for other measures of glu- arm. This lifestyle-associated weight loss was accom- cose control (fasting glucose and insulin, and insulin panied by small reductions in HbA1c at 1 year sensitivity) (21). This is despite very little change in (~ 0.1%) and fasting plasma glucose (~ 5 mg/dl body weight (especially in the aerobic or resistance [0.28 mmol/l]), after which values rose steadily (15).
alone groups; 0–4.6%), but significant reductions in In the Finnish Diabetes Prevention Study (DPS), slightly smaller mean weight losses (4.2 kg; 4.7%),following similar dietary and activity changes for 1 year in patients with IGT, led to a comparable Lifestyle choices are governed by a number of factors, reduction in mean fasting plasma glucose (4 mg/dl including individual biology and psychology, food [0.22 mmol/l]), as well as a mean 5 mmHg reduc- production (packaging, advertising and availability), tion in SBP and DBP (16). After a mean 3.2-year fol- societal influences and the physical environment. Puska low-up, the risk of diabetes development had been et al. proposed that each individual has responsibility reduced by 58% in the lifestyle intervention group for their own lifestyle choices, but that difficulty compared with the control subjects. In these trials, in achieving lifestyle change is directly affected by the the effects of the changes to diet and exercise could individual’s environment (22). Therefore, govern- not be separated; however, the Da Qing IGT and ments and physicians have the power to make lifestyle diabetes study included separate diet, exercise and change easier, and this should be recognised.
diet plus exercise interventions (17). Each type of ‘Nudging’ is a concept of encouraging better intervention resulted in a similar (~ 25%) reduction choices by altering people’s behaviour in a predict- in T2DM incidence at 6 years compared with con- able way without forbidding any options or signifi- trols, suggesting no additive effect of combing diet cantly changing their economic incentives. This might involve making ‘healthy choices’ a default The effect of exercise alone on the risk of CHD (with ‘unhealthy’ options requiring an active deci- was investigated in the Harvard Alumni Health sion), changes to the environment to encourage Study, which followed over 12,000 middle-aged men healthy behaviour (such as introduction of bicycle from 1977 to 1993 (18). A significant ~ 20% reduc- lanes or prominent staircases/hidden elevators) or re- tion in CHD risk was associated with increased phys- organisation of consumer outlets (restaurants, super- ical activity equating to 30 min of brisk walking, markets) to make ‘healthy options’ more prominent cycling, swimming, housework or gardening on most or accessible (23). Nudging appears to be effective in days of the week. For those men who did less exer- shaping small changes in behaviour, and could there- cise (15–30 min/day) there was a non-significant fore be a useful tool in encouraging healthier life- 10% risk reduction, suggesting that even light exer- styles, with respective influence on incidence rates of cise is beneficial, to some extent (18). In support of chronic diseases (T2DM, CVD, cancer) and the this, the Finnish DPS data showed that even low- health care burden. For this reason, nudging is very intensity activity tended towards resolution or pre- popular with politicians as a way to induce positive vention of the cardiometabolic syndrome, but this change, without the need for legislation (24). How- did not reach significance (19). In addition, a pro- ever, the media and retailers utilise nudging for their spective study in Taiwan showed that, compared own benefit, often at the detriment of population with inactive individuals, those who performed light health, by presenting and packaging foods to encourage Int J Clin Pract, April 2013, 67, 4, 322–332 over-consumption, attractively advertising unhealthy • Small increases in physical activity (15–30 min/day of brisk walking/cycling/work around the home) can positively in the media. Effective nudging may, therefore, require collaborative legislation, either to • Environmental and societal influences can have a prevent unhealthy nudges from industry, or to consol- idate the benefit of healthy choices (24). There is a call • Even small changes in smoking habits could result to go one step further to make healthier food choices more affordable, for example by reducing the tax onfruit products (25), or to deter the consumption offat-rich products by increasing the tax on these items, as is currently implemented in Denmark (26).
The role of nudging in improving population health is currently under debate (27,28), with both new In diabetes patients, postprandial glucose (PPG) and research and reanalysis of current evidence required to HbA1c, but not fasting blood glucose (FBG), correlate judge the effectiveness of nudging interventions.
with CVD events and mortality, over the longer term(34,35). Individual prospective studies and a system-atic review of data from 20 randomized trials in T2DM patients have found no conclusive evidence fora reduced risk of death or macrovascular outcomes Introducing a ‘fun factor’ can be effective in modi- following intensive glycaemic control (36,37). How- fying behaviour – researchers in Stockholm turned ever, microvascular complications can be reduced if a subway exit staircase into a working ‘piano’ over- night and noted how many people took the stairs 1c is lowered (36), with the United Kingdom Pro- spective Diabetes Study (UKPDS) reporting a 37% rather than the adjacent escalator. Compared with lower risk of microvascular complications for every the previous day, 66% more people took the stairs.
http://www.thefuntheory.com/piano-staircase 1c reduction (38). Further support for the dichotomy in the response of micro- versus macro-vascular complications to HbA1c is given in a recentreport, showing that within a range of HbA Smoking is a highly significant predictor of CVD rovascular events and death is 7.0% while the thresh- mortality, greatly increasing the CVD mortality risk old for microvascular events is 6.5% (39). A recent, in middle-aged men with and without diabetes (29), large, retrospective cohort study identified 7.5% and doubling the relative risk in an older population (60–79 years) with diabetes, compared with age- 1c as the level that optimally reduced overall mor- tality among T2DM patients (40). These data suggest matched controls (30). Despite this increased risk, the prevalence of smoking in patients with diabetes of life expectancy in decompensated diabetes.
appears to be similar to the global population aver- There is no given definition for a ‘small’ change in CVD risk is substantially reduced following cessa- 1c in the literature, and similarly to body weight, this may be reliant on the baseline level. For the pur- tion of smoking, and this can be detected at a popula- poses of this review, we proposed that 0.5% might be tion level following legislative restrictions (32). CVD considered a small change. However, the evidence for risk reduction appears to depend upon the number of cigarettes per day and the duration of cessation (33).
UKPDS reported an almost linear relationship between Quitting smoking can be considered a big change; however, even reducing consumption could be a valid 1c and the incidence of any diabetes-related end point (any complication, CVD event or death), method for reducing CVD risk, and this is a hypothe- sis that warrants further investigation.
tion in risk for any diabetes-related end point (38). As this relationship was close to linear, we can infer thatsmaller reductions in HbA Obesity is central to the cardiometabolic abnor- lesser risk reduction (a 0.5% HbA1c reduction might yield an ~ 10% risk reduction) (Figure 1). In the • For every 1 kg of body weight lost, the risk of retrospective cohort study identified above, a U-shaped Even small weight losses (2–5%) can improve the was reported (40). Extrapolating this data suggests that a 0.5% reduction in HbA1c, down to the 7.5% thresh- Int J Clin Pract, April 2013, 67, 4, 322–332 old, might relate to a reduction in mortality hazard In diabetes patients, the absolute CVD risk reduction ratio of ~ 0.1, especially in insulin-treated patients gained by lowering BP with diuretic-based antihyper- where the curve was more linear. In IGT patients, rever- tensive treatment was reported to be twice that for sion to normal glucose tolerance has been associated patients without diabetes, reflecting the higher risk of with measurable effects on cardiometabolic risk factors, diabetes patients (47). However, any changes in BP achieved must be maintained by ongoing treatment,as there appears to be no ‘legacy effect’ of previous The prevalence of hypertension among people with T2DM is up to three times higher than in those 2–5 mmHg. The HOT study demonstrated a differ- without diabetes, and is also frequent in patients ence in achieved SBP and DBP of 4 mmHg between with type 1 diabetes (42). For any given person, a lower BP should improve CVD outcomes (43,44), 90 mmHg. This between-group difference in BP and in men with diabetes, the absolute CVD mortal- was associated with no significant difference in the ity risk is around three times higher than for similar incidence of major CVD events in the total study men without diabetes, at any given SBP (29).
population; however, in the sub-population of There is substantial, but circumstantial, evidence patients with diabetes, an ~ 50% reduction in major for non-pharmacological intervention in hyperten- CVD events was observed (49). The ADVANCE trial sion. A modest salt reduction of 2.3–6.9 g/day led to in patients with T2DM revealed that mean SBP and a mean BP reduction of 2 mmHg in normotensive DBP reductions of 5.6 and 2.2 mmHg, respectively, people and 5 mmHg in those with arterial hyperten- were associated with a 9% reduction in the relative sion (45). Observational evidence also suggests that risk of major macro- or micro-vascular events and maintained salt reduction is associated with reduc- an 18% lower relative risk of death from CVD (50).
tions in DBP and stroke mortality (46).
Nonetheless, lowering SBP below 130 mmHg may In general, BP reduction achieved through any bring no further benefit in terms of CVD risk (51).
pharmacological intervention reduces CVD risk (44).
In the ACCOMPLISH study, which included 11,506 Figure 1 Incidence rate for any end point related to T2DM* according to updated mean HbA1c. The black curverepresents the adjusted incidence rate with 95% confidence intervals (error bars). The grey solid and dashed lines representthe inferred change in incidence rate with each 0.5% reduction in HbA1c.
*Adjusted for age, sex and ethnic group, for white men aged 50–54 years at diagnosis and with mean duration of diabetesof 10 years.
Reproduced from Stratton et al. 2000 (38), with permission from BMJ Publishing Group Ltd.
Int J Clin Pract, April 2013, 67, 4, 322–332 participants (~ 60% of whom had diabetes), a • 1.0 mmol/l reductions in LDL can decrease all- between-treatment difference in SBP/DBP of 0.9/ cause mortality by 10%. Small changes in HDL and 1.1 mmHg was associated with a 2.2% absolute risk TG alone may have an effect, but small improve- reduction and a 19.6% relative risk reduction for a ments in the combined lipid profile could bring composite end point of major CVD events (52). The HOPE study included 9297 participants at high riskof CVD events (~ 38% of whom had diabetes).
Here, a between-treatment difference in SBP/DBP of 3/2 mmHg after two years was associated with a22% relative risk reduction for myocardial infarction, stroke or death from cardiovascular cause and a 26% In order to effectively support change, as physicians, relative risk reduction in cardiovascular mortality.
we need to take a patient-centred approach. To The extent of this benefit may be attributable, in achieve realistic goals, we must understand and work part, to the vasculoprotective effects of angiotensin- with the objectives, needs and fears of the patient (59–63). Clinical tools can assist the physician inmotivating their patients to change, including coun- selling and motivational interviewing (64,65). These Dyslipidaemia is a major risk factor responsible for tools can help patients to accept the influence of driving CVD, and much of this risk is accounted for their lifestyle choices on their health, and to improve by increased LDL levels, although many CVD events their motivation to change (66). The impact of a occur despite optimal LDL control. Evidence suggests positive physician attitude towards a patient’s capac- that abnormal lipid profiles are already present in a ity to change shouldn’t be underestimated, and phy- number of young adults and children, with one study reporting that ~ 10% of children had raised motivation) should continue at regular intervals over LDL levels ( 130 mg/dl; 3.36 mmol/l) (54).
With such a strong CVD association, small changes One such approach to engage patients in manage- in LDL levels (of 0.1–1.0 mmol/l; ~ 4–40 mg/dl) and ment of their disease is ‘Therapeutic Patient Educa- other lipid parameters may have a real impact on tion’ (TPE), which has been endorsed by the World patient health, especially if realised early.
Health Organization since 1998 (67). This concept In a meta-analysis of 26 clinical trials, a 1.0 mmol/l aims to train patients in the skills they require to reduction in LDL was associated with a 10% reduc- self-manage their chronic condition, to adapt treat- tion in all-cause mortality, largely due to fewer deaths ment to their individual needs, and to foster support from CHD and other cardiac causes (55). It has also from their families and friends. In this way, patients been shown that the absolute change in LDL, rather can take ownership of their disease management, than the baseline level, has the prognostic impact for improve their quality of life, and prevent avoidable CHD risk reduction (56). Increases in HDL from low complications. The benefits of this approach have levels do not appear to exert an impact on CVD been demonstrated in an analysis of ~ 600 studies of parameters, and specifically on atheroma volume, patient education in chronic disease, which found a until reaching at least a moderate, threshold level significant positive effect of TPE in 64% cases (60).
(57). With further increases, small changes might Evidence-based guideline targets are important to influence the number of CVD events (57,58). It has strive for, but on the path to achieving these we not been shown that either small or larger changes in should acknowledge the benefits of each small TG levels alone influence the number of ischaemic change and reinforce the positive benefits of each events; however, TG and HDL changes in combina- ‘small step’ for the patient. A ‘realistic’ 80/20 lifestyle tion with LDL lowering may have greater effect.
might be recommended, whereby the patient shouldcommit fully to their lifestyle changes 80% of the Summary – Small changes in cardiometabolic time, with a 20% ‘buffer’ for special occasions (for example holidays and birthdays). This may help toavoid relapses.
• A 0.5% HbA1c reduction may lead to an ~ 10% risk reduction for any diabetes-related end point and Measurement of small changes in most of the dis- • Small reductions in BP of 2–5 mmHg may lower cussed parameters is straight-forward – accurate relative risk of CVD death by at least 18% in patients laboratory tests and body weight measurements are Int J Clin Pract, April 2013, 67, 4, 322–332 However, practical or visual demonstrations of the population and individual approaches are not mutu- effect of lifestyle or treatment changes may be a ally exclusive, but complementary. A population stronger influence on patient motivation than ‘numbers’.
approach will not be effective if active services for For example, a patient may not have lost much body high-risk individuals do not exist, and individual weight, but may have toned; allowing them to fit treatment of those at high risk will not be effective if into a smaller clothes size, which is a better reward the general population are not fully informed and Measurement of intima media thickness (IMT), which describes changes in the thickness of the intima and media of the carotid artery, is performed Small changes in lifestyle in patients with cardiomet- non-invasively by ultrasonography. IMT measure- abolic disease can be seen to have a positive impact ment is now recognised as a promising tool for on costs from a long-term, as well as a short-term, improved management of disease (54). The American perspective (81–83). In addition, the cost efficacy of Heart Association recommend IMT measurement for small changes following medical therapy can be dem- individual risk stratification (68), and IMT assess- onstrated: In a lipase inhibitor study, the reported ment has been shown to improve CVD risk classifi- cost efficacy value for patients responding to treat- cation in a number of populations (69,70). This ment (according to the pre-defined study criteria of technique allows visualisation of the morphologic 5% body weight reduction within 12 weeks) was alterations in the carotid artery wall, and offers an well within the limits of what countries with an offi- integrated view of risk factors, as defined by the cial threshold consider cost-effective. Changing the Mannheim consensus (71). The single components of the cardiometabolic syndrome, such as arterial ( 3%) had only a limited impact, returning a rela- hypertension, hypertriglyceridaemia and hyperinsuli- tively similar cost-effectiveness to that estimated for naemia, are associated with varying increases in IMT, as shown in the ARIC study, but act synergistically if Nevertheless, caution in interpretation of health all are present in an single individual (72).
economic analyses must be exercised. Comparison of As a clinical tool, IMT evaluation effectively effects between different studies is complicated by records physiological improvements following lifestyle compilation of data from different sources within a or treatment alterations (73–76), and as a visual tool model framework, the use of different assumptions it may aid the physician in demonstrating to the between models and the choice of modelling tech- patient the effects of their efforts and in monitoring nique, which can lead to very different results, even their progress over the longer term. Age, body weight, if based on data from the same clinical study body composition and physical activity all strongly (81,82). Although not perfect, many issues arising influence the cardiovascular morphology and IMT in from health economic modelling might be, at least a healthy population, as demonstrated in the RISC partially, avoided if studies included resource-use study (77–79). This technique is also sensitive enough data or cost data as direct end-points.
to provide a valuable tool for research into the car-diovascular benefits of small changes, allowing 0.01 mm changes in the vessel wall to be defined.
individualisationSmall lifestyle and treatment changes can have a sig- nificant impact on short- and longer-term outcomes We face the ‘prevention paradox’ described by Geof- and, as described above, this can be observed in the frey Rose in 1981 (80), whereby a large change in the data from a number of international trials and meta- risk of high-risk individuals has a great impact on analyses. Although cultural factors greatly influence the lives of those individuals, but little effect on the lifestyle changes, these findings have been consistent health of the population as a whole; however, the benefits of a ‘population approach’, whereby every- Improving health in ‘small steps’ may change body receives a small benefit, can be unexpectedly patient perception of the effort required to achieve a large. In other words, a small change in a number of bigger change. Small, sustained changes to everyday people can have a very large overall effect. In terms life can go relatively unnoticed, but may have a of patient motivation to change, population level substantial impact. For example, cutting out one changes can be hard to implement, as the benefit for 50 kcal snack per day might yield an ~ 1 kg weight each individual is small, as is the immediate reward.
loss over a year. Likewise, expending 50 kcal of It is much easier to encourage change on an individ- energy each day by walking 1 km might have the ual level, but this brings less population benefit. The Int J Clin Pract, April 2013, 67, 4, 322–332 One-year data from the Finnish DPS showed that • Small changes in lifestyle and treatment have each individual lifestyle target achieved was associ- shown cost benefits, but economic modelling should ated with a considerable reduction in the risk of dia- betes development, but that in the intervention • Small changes individually may have an effect, but group, each additional target reached dramatically combining a number of small changes is likely to reduced the incidence of diabetes further, with a risk of almost zero for those achieving four of five targets(Figure 2) (16). Therefore, whilst small changes in lifestyle parameters individually may have a smallbut significant impact on health, small changes in Common sense dictates that some change is better than multiple parameters together are likely to have a lar- no change. In this review of the literature evidence for the effect of ‘small’ changes in the management of dia- With an increasing demand for ‘personalised med- betes and cardiometabolic disorders, we have high- icine’, it might be proposed that physicians consider lighted that significant effects on body weight and a list of recommended small changes, and suggest a cardiometabolic parameters really can be observed, and varying number of these to any given patient accord- that greater benefit is likely to be achievable by making ing to their individual risk profile and ability or a number of small changes together. In trying to attain guideline-recommended targets, we should recognisethe value of each small change for patient outcome.
Summary – Perspectives for clinical practice Physicians must recognise their influence on patientmotivation, and utilise the clinical tools at their dis- • Patient engagement is essential – physicians should posal to engage with individual patients, and encourage recognise their influence and work with patients to their commitment to further change. At the same time, choose realistic goals and gain commitment to change.
• Clinical tools such as motivational interviewing changes in a large number of people, should be encour- and IMT measurement may be helpful to improve aged, to maximise potential benefits.
While our definitions of ‘small’ change may be • Population-based and individual approaches to slightly subjective, we believe that the concept of implementing small change should be combined for reaching recommended targets ‘step-by-step’, by implementing less noticeable changes a few at a time, Figure 2 Incidence of T2DM at 1-year follow-up, according to the number of lifestyle intervention goals achieved.
Reproduced from Tuomilehto et al. 2001 (16), with permission from the Massachusetts Medical Society.
Int J Clin Pract, April 2013, 67, 4, 322–332 and ensuring that each step represents a reward for the article. ML: Concept/design, data review/interpreta- patient in terms of positive impact on outcomes and tion, critical revision of article, approval of article.
encouragement to continue, may aid the clinical man- GM: Concept/design, data review/interpretation, crit- agement of cardiometabolic disorders. However, this ical revision of article, approval of article. JP: Con- approach is not restrictive, and may be of value to other groups of people, including the asymptomatic revision of article, approval of article. T-MP: Critical overweight and patients in other disease areas. We revision of article, approval of article. KP: Concept/ believe that more research is warranted into the effects design, data review/interpretation, critical revision of of making small changes on patient outcomes.
article, approval of article. C-HA: Concept/design,data review/interpretation, critical revision of article, drafting article, critical revision of article, approval ofarticle. EB: Data review/interpretation, critical revi- The authors would like to thank Novo Nordisk sion of article, approval of article. RG: Concept/ Region Europe A/S for funding an author meeting to design, data review/interpretation, critical revision of discuss this manuscript. Editorial support was pro- article, approval of article. TK: Concept/design, data vided by Claire Price of PAREXEL International, and this support was funded by Novo Nordisk Region approval of article. NL: Concept/design, data review/ interpretation, critical revision of article, approval of mised controlled trial of high-protein versus high- 20 Wen CP, Wai JP, Tsai MK et al. Minimum amount carbohydrate diets over 2 years in type 2 diabetes.
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Clomiphene citrate and intrauterine insemination:analysis of more than 4100 cyclesSerena Dovey, Rita M. Sneeringer, M.D.,,and Alan S. Penzias, a Boston IVF, Waltham, Massachusetts; b Division of Reproductive Endocrinology and Infertility, Department of Obstetrics andGynecology, Beth Israel Deaconess Medical Center, Boston, Massachusetts; and c Harvard Medical School, Boston,MassachusettsObjecti